As a process for preparing N,O-dialkylhydroxycarbamic acid ester from hydroxylamine or its salts, a process comprising reacting chloroformic acid ester with a salt of hydroxylamine in the presence of sodium hydroxide and subsequently reacting the reaction solution with dialkyl sulfate in the presence of sodium hydroxide is known generally.
For example, a process disclosed in Org. Prep. Proced. Vol. 19, P. 75 (1987)! is known as a process for preparing ethyl N,O-dimethylhydroxycarbamate. According to this process, hydrochloride of hydroxylamine is reacted with ethyl chloroformate using a sodium hydroxide solution to obtain ethyl hydroxycarbamate, and then dimethylating this product with dimethyl sulfate and a sodium hydroxide solution to obtain ethyl N,O-dimethylhydroxycarbamate in a 70-73% yield.
With respect to butyl N,O-dimethylcarbamate, a process disclosed in the specification of West German Patent Application Laid-open No. 3,245,503 is known. This process comprises reacting sulfate of hydroxylamine as a starting material with butyl chloroformate in the presence of sodium hydroxide, extracting the reaction product with dichloromethane, drying the extract, distilling the solvent away from the dried extract to obtain butyl hydroxycarbamate and dimethylating this product using dimethyl sulfate and a sodium hydroxide solution to obtain ethyl N,O-dimethylhydroxycarbamate in the total yield of 65%.
However, the processes which had been reported so far was disadvantageous in that they give the aimed N,O-dialkylhydroxycarbamic acid ester in low yields in order to perform industrially. In addition, the above processes, according to the study by the present inventors, have been found to be disadvantageous in the case of carbamoylating hydroxylamine or its salt with methyl chloroformate and then dialkylating the resulting product to prepare N,O-dialkylhydroxycarbamate in that methyl chloroformate to be used as a carbamoylating agent is liable to be hydrolyzed because this reaction is carried out using an aqueous solution as a solvent and the yield of the aimed product becomes further low because a hydroxyl group of methyl hydroxycarbamate as the formed intermediate reacts with methyl chloroformate, as will be mentioned in Referential Example 1.
Furthermore, as a process for preparing N,O-dimethylhydroxylamine, for example, a process comprising obtaining the same through sulfonimide which is obtained by reacting nitrite, hydrogensulfite and SO2, as is disclosed in the specification of French Patent Application Laid-open No. 1,377,470, or the like is generally known. However, this process is disadvantageous for an industrial process because a large quantity of waste fluid is brought about.
As a method for recovering N,O-dimethylhydroxycarbamic acid ester, a method comprising extracting N,O-dimethylhydroxycarbamic acid ester with an organic solvent such as halogenated hydrocarbon or the like can be enumerated. From the viewpoint of environmental problems, however, a more effective method is desired. In addition, because O-methylhydroxylcarbamic acid ester, which is formed as impurities in the course of the formation reaction of N,O-dimethylhydroxycarbamic acid ester, is also extracted, O-methylhydroxyamine is contained in N,O-dimethylhydroxylamine obtained after deprotection. Boiling points of these compounds are so close as 42.3.degree. C. for N,O-dimethylhydroxylamine and 48.1.degree. C. for O-methylhydroxylamine, so that it is very difficult to purify the same by distillation and a multi-stage distillation column is required for separation.
As a method for purifying N,O-dimethylhydroxylamine, the specification of U.S. Pat. No. 3,230,260 discloses a method for removing O-methylhydroxylamine which comprises reacting O-methylhydroxylamine contained in N,O-dimethylhydroxylamine with formaldehyde at a pH 7 or lower to prepare gaseous O-methylformaldehyde oxime and removing it.
In order to remove O-methylhydroxylamine according to the method disclosed in the specification of U.S. Pat. No. 3,230,260, such complicated steps as once extracting N,O-dimethylhydroxycarbamic acid ester as an intermediate and a reaction product, e.g., O-methylhydroxycarbamic acid ester from an aqueous solution containing inorganic salts and the like using an organic solvent such as halogenated hydrocarbon or the like, carrying out deprotection after concentrating the extracted solvent, reacting the resulting solution with formaldehyde to prepare gaseous O-methylformaldehyde oxime and separating this must be gone through. In addition, a halogenated hydrocarbon solvent to be used in the extraction step and formaldehyde to be used in the reaction are both highly toxic. Particularly, formaldehyde has such low legal permissible concentration as 2 ppm and thus is a substance very difficult to handle. Furthermore, O-methylformaldehyde oxime to be formed has a problem that, because its boiling point is as low as -12.degree. C., an apparatus having high cooling efficiency is necessary for its recovery and thus it will cost a great deal for an apparatus and complicated steps.
As a process for preparing N,O-dialkylhydroxylamine from N,O-dialkylhydroxycarbamic acid ester, a process of hydrolyzing the ester in the presence of hydrochloric acid as a catalyst in an aqeuous solution is generally adopted. For example, in West German Patent Application Laid-open No. 3,245-503, butyl N,O-dimethylhydroxycarbamate was hydrolyzed with hydrochloric acid, concentrated and evaporated to dryness to obtain N,O-dimethylhydroxylamine hydrochloride. In Org. Prep. Proced. Vol. 19, P. 75 (1987)!, ethyl N,O-dimethylhydroxycarbamate as hydrolyzed with hydrochloric acid and the hydrolysate was azeotropically dehydrated using isopropanol to obtain N,O-dimethylhydroxylamine hydrochloride. However, these process, because of using an acid as a catalyst, require a hydrochloric catalyst beyond stoichiometry in order that the formed N,O-dimethylhydroxylamine forms a salt with hydrochloric acid. In addition, in order to recover the obtained N,O-dimethylhydroxylamine hydrochloride in an anhydrous state, such complicated post-treatment as disclosed in Org. Prep. Proced. Vol. 19, P. 75 (1987)! is required. Therefore, these cannot be industrial processes for preparation. Furthermore, in case of aiming to obtain free N,O-dimethylhydroxylamine, alkali equivalent or more to hydrochloric acid used is required for neutralization and thus the process comes to bring out a great deal of waste fluid. Incidentally, although there can be a process using sulfuric acid as a catalyst instead of hydrochloric acid, side-reaction takes place to lower the purity of N,O-dimethylhydroxylamine (see Comparative Example 2).
Generally, N,O-dialkylhydroxylamine can be obtained according to a process comprising using hydroxylamine as a starting material, converting the same into hydroxycarbamic acid ester and dialkylating or deprotecting the ester; a process comprising using nitrite as a starting material, reacting hydrogensulfite with SO2 and, according to demand, repeating alkylation and hydrolysis; etc. According to these processes, however, O-alkylhydroxylamine is contained in the obtained N,O-dialkylhydroxylamine as impurities, so that it become necessary to remove O-alkylhydroxylamine from N,O-dialkylhydroxylamine. In this respect, there is a description about it in the specification of U.S. Pat. No. 3,230,260 as aforementioned, and it has the aforementioned problems.
With respect to a method for separating N,O-dimethylhydroxylamine hydrochloride, the following two methods have been reported so far.
One is a method disclosed in the specification of West German Patent Application Laid-open No. 3,245,503, according to which a solution of N,O-dimethylhydroxylamine obtained by hydrolyzing butyl N,O-dimethylhydroxycarbamate with concentrated hydrochloric acid was evaporated to dryness to quantitatively obtain hydrochloride of N,O-dimethylhydroxylamine.
The other is a method disclosed in Org. Prep. Proced. Vol. 19, P. 75 (1987)!, which comprises decomposing ethyl N,O-dimethylhydroxycarbamate with concentrated hydrochloric acid, removing most of water using a rotary evaporator, performing azeotropic dehydration by adding 2-propanol to the resulting product in order to remove moisture completely, repeating this operation 6 times, filtering crystals after adding 2-propanol to the dehydrate, drying the crystals, thereby obtaining hydrochloride of N,O-dimethylhydroxylamine in a 93-95% yield.
However, the present inventors supplementarily examined the method of evaporation to dryness disclosed in the specification of West German Patent Application Laid-open No. 3,245,503. In this supplementary examination, the solvent was distilled away using a rotary evaporator at a bath temperature of 60.degree. C. under a pressure of 40 mmHg and the resulting product was further dried at room temperature at a pressure of 1 mmHg for 10 hours. As the result, it was found that the moisture content of the obtained crystal was 11% and thus it was difficult to completely remove moisture in the crystal. In addition, it is difficult to take out the crystal obtained by evaporation to dryness from a container use for drying, so that it is difficult to perform this method industrially.
On the other hand, as a result of supplementarily examining the method disclosed in Org. Prep. Proced. Vol. 19, P. Y5 (1987)!, the present inventors confirmed that N,O-dimethylhydroxylamine hydrochloride could be obtained in the yield given in the above literature. However, not only because the procedures of this method is very complicated but also because 2-propanol forms an azeotrope with water and is miscible with water, the recovery of a solvent used becomes low. Accordingly, it is difficult to perform this method industrially from the viewpoint of economy.
It is the first object of the present invention to provide a process for preparing N,O-dialkylhydroxycarbamic acid ester in yields higher than the conventional processes.
It is the second object of the present invention to provide a process for recovering N,O-dialkylhydroxycarbamic acid ester as an intermediate of N,O-dialkylhydroxylamine selectively, more readily and safely than the conventional processes to obtain N,O-dialkylhydroxylamine as the final aimed product.
It is the third object of the present invention to provide a process for industrially advantageous preparation of N,O-dialkylhydroxylamine which comprises hydrolyzing N,O-dialkylhydroxycarbamic acid ester by using an alkali to form N,O-dialkylhydroxylamine without forming its salt.
It is the fourth object of the present invention to provide a method for removing O-alkylhydroxylamine hydrochloride contained in N,O-dialkylhydroxylamine hydrochloride, which is not only safer than the conventional methods but also enable easy recovery of O-alkyl oxime.
It is the fifth object of the present invention to provide a method for separating N,O-dialkylhydroxylamine hydrochloride, which is simpler and easier than the conventional separation methods and enables the recovery of a solvent used in high yields.